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Abstract
Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health.
Highlights
The skin is colonized by a diverse array of microorganisms including bacteria and fungi
S. lugdunensis and C. parapsilosis (105 colony forming unit (CFU)/ml) isolated from human dandruff flakes was incubated in rich media in the absence and presence of 20 g/l glycerol, 0.0005% mPEG diluted in water, or 0.0005% mPEG-PCL dissolved in 0.5% acetone at 37°C
To examine the fermentation activities of these bacteria and fungi, each individual microbe was incubated in rich media in the presence of 20 g/l glycerol, a naturally occurring metabolite found in human skin [29], as the carbon source
Summary
The skin is colonized by a diverse array of microorganisms including bacteria and fungi. The dysbiosis of bacterial-fungal populations has been implicated in scalp dandruff, which presents as significant problems to large numbers of people [4]. Besides dysfunction of the skin barrier and sebaceous gland, fungal/bacterial dysbiosis may be one of the factors that result in the progression of human dandruff. Bacteriotherapy, in which commensal bacteria as probiotics are used to rein in the over-growth of opportunistic microbes, has been shown to be a promising modality for normalization of dysbiosis in the human microbiome [8,9,10,11,12,13,14]. The significance in this study includes providing a brand new approach to treat the fungal infection of the scalp skin, thereby benefiting the entire community of patients with dandruff or seborrheic dermatitis. Fermenting S. lugdunensis bacteria and their ferment metabolites may be novel therapeutics for the treatment of C. parapsilosis-associated infections
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